There are a large range of diseases and therapies of the heart that can benefit from the information provided by a high-resolution, real time imaging modality. Diseases and abnormalities of the myocardium are due to problems of the heart muscle, ranging from infections to abnormalities in conduction, structure, and contraction. For these conditions, catheters are inserted into the heart chambers, without a direct view of the heart wall to obtain electrical measurements, take biopsies to detect cellular changes, or delivery energy to treat arrhythmias. It is our goal to develop tools for imaging the myocardium, which will provide cardiac electrophysiologist, cardiologist, and heart surgeons a view of the heart wall to aid in disease diagnosis and guide therapy. Our objective is to develop high-resolution optical imaging modalities and image analysis for diagnosis and therapy monitoring of diseases of the heart wall. Applications of optical imaging in the myocardium range from assessment of transplant rejection by preforming an optical biopsy to monitoring radiofrequency ablation therapy. This DP2 New Innovator proposal focuses on establishing a platform imaging modality including designing optical catheters and developing classification algorithms for real time imaging of the myocardium in the cardiovascular and cardiac electrophysiology laboratory. We aim to demonstrate that OCT can address unmet clinical needs of cardiac imaging by providing cellular-level imaging of the myocardium. Our approach is multi-scaled including: developing high resolution OCT system with and without polarization sensitivity optimized for myocardial imaging, and prototyping high resolution catheters to perform optical biopsy and provide three dimensional imaging of myocardial substrates. We will evaluate the new technology developed on human myocardial tissue ex vivo with and without the presence of blood.